17.1 Physical Defenses

Nonspecific innate immunity provides a first line of defense against infection by nonspecifically blocking entry of microbes and targeting them for destruction or removal from the body.
The physical defenses of innate immunity include physical barriers, mechanical actions that remove microbes and debris, and the microbiome, which competes with and inhibits the growth of pathogens.
The skin, mucous membranes, and endothelia throughout the body serve as physical barriers that prevent microbes from reaching potential sites of infection. Tight cell junctions in these tissues prevent microbes from passing through.
Microbes trapped in dead skin cells or mucus are removed from the body by mechanical actions such as shedding of skin cells, mucociliary sweeping, coughing, peristalsis, and flushing of bodily fluids (e.g., urination, tears)
The resident microbiota provide a physical defense by occupying available cellular binding sites and competing with pathogens for available nutrients.

17.2 Chemical Defenses

Numerous chemical mediators produced endogenously and exogenously exhibit nonspecific antimicrobial functions.
Many chemical mediators are found in body fluids such as sebum, saliva, mucus, gastric and intestinal fluids, urine, tears, cerumen, and vaginal secretions.
Antimicrobial peptides (AMPs) found on the skin and in other areas of the body are largely produced in response to the presence of pathogens. These include dermcidin, cathelicidin, defensins, histatins, and bacteriocins.
Plasma contains various proteins that serve as chemical mediators, including acute-phase proteins, complement proteins, and cytokines.
The complement system involves numerous precursor proteins that circulate in plasma. These proteins become activated in a cascading sequence in the presence of microbes, resulting in the opsonization of pathogens, chemoattraction of leukocytes, induction of inflammation, and cytolysis through the formation of a membrane attack complex (MAC).
Cytokines are proteins that facilitate various nonspecific responses by innate immune cells, including production of other chemical mediators, cell proliferation, cell death, and differentiation.
Cytokines play a key role in the inflammatory response, triggering production of inflammation-eliciting mediators such as acute-phase proteins, histamine, leukotrienes, prostaglandins, and bradykinin.

The formed elements of the blood include red blood cells (erythrocytes), white blood cells (leukocytes), and platelets (thrombocytes). Of these, leukocytes are primarily involved in the immune response.
All formed elements originate in the bone marrow as stem cells (HSCs) that differentiate through hematopoiesis.
Granulocytes are leukocytes characterized by a lobed nucleus and granules in the cytoplasm. These include neutrophils (PMNs), eosinophils, and basophils.
Neutrophils are the leukocytes found in the largest numbers in the bloodstream and they primarily fight bacterial infections.
Eosinophils target parasitic infections. Eosinophils and basophils are involved in allergic reactions. Both release histamine and other proinflammatory compounds from their granules upon stimulation.
Mast cells function similarly to basophils but can be found in tissues outside the bloodstream.
Natural killer (NK) cells are lymphocytes that recognize and kill abnormal or infected cells by releasing proteins that trigger apoptosis.
Monocytes are large, mononuclear leukocytes that circulate in the bloodstream. They may leave the bloodstream and take up residence in body tissues, where they differentiate and become tissue-specific macrophages and dendritic cells.

Phagocytes are cells that recognize pathogens and destroy them through phagocytosis.
Recognition often takes place by the use of phagocyte receptors that bind molecules commonly found on pathogens, known as pathogen-associated molecular patterns (PAMPs).
The receptors that bind PAMPs are called pattern recognition receptors, or PRRs. Toll-like receptors (TLRs) are one type of PRR found on phagocytes.
Extravasation of white blood cells from the bloodstream into infected tissue occurs through the process of transendothelial migration.
Phagocytes degrade pathogens through phagocytosis, which involves engulfing the pathogen, killing and digesting it within a phagolysosome, and then excreting undigested matter.

Inflammation results from the collective response of chemical mediators and cellular defenses to an injury or infection.
Acute inflammation is short lived and localized to the site of injury or infection. Chronic inflammation occurs when the inflammatory response is unsuccessful, and may result in the formation of granulomas (e.g., with tuberculosis) and scarring (e.g., with hepatitis C viral infections and liver cirrhosis).
The five cardinal signs of inflammation are erythema, edema, heat, pain, and altered function. These largely result from innate responses that draw increased blood flow to the injured or infected tissue.
Fever is a system-wide sign of inflammation that raises the body temperature and stimulates the immune response.
Both inflammation and fever can be harmful if the inflammatory response is too severe.